This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this project is to identify biomarkers that are individually, and in combination, associated with diverse forms of life challenges and psychological and social factors characterizing persons from young adulthood into old age. Cumulative adversity with limited compensating advantages is hypothesized to be reflected in multiple biological indicators of dysregulation. Conversely, the maintenance of high levels of well-being in the face of life's challenges is hypothesized to be reflected in biological indicators of high levels of functioning across multiple systems. Biomarker data collection will be carried out at 3 General Clinical Research Centers (at UCLA, University of Wisconsin, and Georgetown University) on a sub-sample of the MIDUS population (N=1350) and on a sub-sample of the Milwaukee African-American sample (N=200). The biomarkers reflect functioning of the hypothalamic-pituitary axis, the autonomic nervous system, the immune system, cardiovascular system, and metabolic processes. In addition to average/resting levels of such biomarkers, a laboratory cognitive and orthostatic challenge study is accompanied by assessments of salivary cortisol over time, heart-rate variability, and blood pressure dynamics. The quality of interpersonal relationships, the structuring of work experience and associated opportunities (or the lack thereof) for career advancement, a personal sense of purpose and growth, and the possession (or lack thereof) of effective strategies for management of diverse and often unanticipated life challenges are all phenomena that have been associated with biological responses, usually focused on one, or at most two, measures at a time. We will assess associations between responses on multiple biomarkers individually, and in combination, with individual challenges and complex profiles reflecting cumulative challenges and a diversity of psychosocial factors and health characteristics. The integration of evidence about psychosocial and biological interrelationships facilitates understanding of the factors associated with resilience and the maintenance of high levels of functioning. This, in turn, can provide a more rigorous foundation for multi-faceted health promotion programs in the future and facilitate understanding of the pronounced declines in disability among the elderly that have been occurring over the past two decades.